Our studies in the rabbit have shown that the young appendix is an important site of development of the cells destined to produce protective antibodies. The rabbit appendix has functions similar to those of the avian bursa of Fabricius. In the young rabbit, there is rapid growth and expansion of B lymphocytes in the appendix, and positive and negative selection events occur. We believe that the cells that survive selection in the appendix seed the peripheral lymphoid system and undergo self renewal to maintain the primary repertoire. The data on rabbit led us to study the role of human appendix and GALT in development of the human immune repertoire and mucosal immunity. We compared development of normal human appendix germinal centers (GC) with rabbit appendix GC development at different ages. In both human and rabbit appendix, we found that lymphoid follicles were just beginning to form at birth. Germinal centers became evident at about 1 month in human and at 1 week in rabbit appendix. Most lymphoid development occurred within the first year in the human and within the first 12 weeks in the rabbit appendix. Lymphoid tissue began to atrophy by adulthood in both human and rabbit appendix. The follicles became smaller and fewer in number whereas the connective tissue and smooth muscle increased. The appendix did not entirely involute; germinal centers were still present in 5 human samples from individuals 75 years or older and in 6- and 7 yr-old rabbit specimens. The human appendix shares some characteristics of a "mammalian bursa equivalent"; it is a B-cell rich organ in the young and the morphology of the follicles and GC changes with age. The human appendix is similar in many respects to the rabbit appendix, avian bursa and sheep ileal Peyer's patch, yet several differences exist. The GC structure and relative GC T-cell density of the human appendix throughout development differs from that of the rabbit appendix and chicken bursa which could indicate that human appendix is more similar to a peripheral than central lymphoid organ. However, it is possible that peripheral lymphoid organs share some central lymphoid function. Whether this is true for the human appendix and other GALT warrants further investigation. Molecular studies of sequences of genes encoding antibody heavy and light chain are in progress (see Z01 AI00226-19 LI) to further investigate whether the appendix of man plays any role as a primary lymphoid organ.(J. Dasso et al., 2000).A clinical research protocol (#OH99-I-N026) entitled, "Effect of Appendectomy on Mucosal Immunity in Children" was reviewed and approved by the IRBs of Children's National Medical Center, and NIAID, NIH. I terminated this study as of July 29, 2000 because of low numbers of patients accrued and our inability to carry through the arm of the study that would have analyzed responses to oral polio vaccine. A paper describing the methods developed to prepare and assay patient samples and some preliminary results is in preparation (J. Dasso et al., ms in preparation).